This is an application from the Joslin Diabetes Center/Children?s Hospital, a current Diabetes Prevention Trial-1 (DPT-1) Clinical Center to become a Clinical Center in the national diabetes trial network for Type 1 diabetes mellitus, the TrialNet. TrialNet, a national network of cooperative clinical research groups will consist of clinical centers and core support facilities. Its common goal will be to perform intervention studies to prevent, treat or ameliorate Type 1 diabetes mellitus in humans. TrialNet will also support natural history and genetic studies in the population screened or enrolled in specific studies aiming to achieve a better understanding of the etiology and pathogenesis of Type 1 diabetes and to develop strategies to prevent the disease. The Joslin Diabetes Center/Children?s Hospital proposed TrialNet Clinical Center includes expanded resources in experienced personnel, in addition to the expanded network of associated institutions to the collaborative effort led by the NIH. Our Clinical Center will have two major objectives: 1.) to complete the ongoing DPT-1 study; 2.) to participate in the design and implementation of existing and future pilot and expanded studies of new agents to prevent, treat or ameliorate Type 1 diabetes mellitus and also to participate and provide resources for genetic and natural history studies. The ongoing Diabetes Prevention Trial for Type 1 Diabetes (DPT-1) is testing, whether early intervention with parenteral or oral insulin in nondiabetic relatives of persons with Type 1 diabetes with increased risk for the disease can delay the clinical onset of Type 1 diabetes. The DPT-1 is currently funded through August 2001 and the TrialNet will be entrusted to carry on and complete the current protocol. Our Joslin/Children?s center is committed to contribute to future clinical studies in Type 1 diabetes mellitus. We also propose a novel interventional protocol, using insulin B-chain in incomplete Freund?s adjuvant in newly diagnosed Type 1 diabetes patients to test its preventive effect in beta cell function decline. The primary outcome measure is mixed meal stimulated C-peptide levels. Phase 1 part of the study is currently underway.